Vitiligo is a disease in which benign pigment cells within the skin are destroyed. Melanomas, the biologic opposite of vitiligo, are a malignant proliferation of the same cell line. In horses, swine and humans these two diseases commonly occur together within the same host. The frequency of their association suggests the relationship is not accidental. If the mechanisms which cause vitiligo could be identified, they might be useful to destroy malignant pigment cells. We present two hypotheses to explain the pathogenesis of vitiligo in association with melanoma. The first proposes that precursors of melanin may be toxic to pigment cells; the second suggests immune mechanisms may be the killer. We have outlined one series of experiments to test in vitro the toxicity of melanin precursor or chemically related compounds for malignant pigmnet cells. Those compounds highly toxic to melanocytes in vitro will be utilized to produce vitiligo in mice with a dark pelage and possibly to destroy malignant cells in mice bearing melanomas. In a second series of investigations we shall attempt to induce vitiligo in mice by manipulation of the immune system, and by in vitro techniques confirm the presence of a cellular and/or humoral immune reaction against antigens common to benign and malignant melanocytes. The applicability of this project to human subjects with metastatic melanoma is discussed.